Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation.

Background: Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC.

Methods: A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0.

Results: Over four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01-2.77), though it was attenuated after adjustment for body mass index.

Conclusions: The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years.